title: The origin of human mesenchymal stromal cells dictates their reparative properties.
abstract: BACKGROUND
  Human mesenchymal stromal cells (hMSCs) from adipose cardiac tissue have attracted considerable interest in regard to cell-based therapies. We aimed to test the hypothesis that hMSCs from the heart and epicardial fat would be better cells for infarct repair.
  
  
  RESULTS
  We isolated and grew hMSCs from patients with ischemic heart disease from 4 locations: epicardial fat, pericardial fat, subcutaneous fat, and the right atrium. Significantly, hMSCs from the right atrium and epicardial fat secreted the highest amounts of trophic and inflammatory cytokines, while hMSCs from pericardial and subcutaneous fat secreted the lowest. Relative expression of inflammation- and fibrosis-related genes was considerably higher in hMSCs from the right atrium and epicardial fat than in subcutaneous fat hMSCs. To determine the functional effects of hMSCs, we allocated rats to hMSC transplantation 7 days after myocardial infarction. Atrial hMSCs induced greatest infarct vascularization as well as highest inflammation score 27 days after transplantation. Surprisingly, cardiac dysfunction was worst after transplantation of hMSCs from atrium and epicardial fat and minimal after transplantation of hMSCs from subcutaneous fat. These findings were confirmed by using hMSC transplantation in immunocompromised mice after myocardial infarction. Notably, there was a correlation between tumor necrosis factor-α secretion from hMSCs and posttransplantation left ventricular remodeling and dysfunction.
  
  
  CONCLUSIONS
  Because of their proinflammatory properties, hMSCs from the right atrium and epicardial fat of cardiac patients could impair heart function after myocardial infarction. Our findings might be relevant to autologous mesenchymal stromal cell therapy and development and progression of ischemic heart disease.
authors.affiliation: Leviev Heart Center, Sheba Medical Center, Tamman Cardiovascular Research Institute, Tel-Hashomer, Israel.
authors.forename: Nili
authors.initials: N
authors.lastname: Naftali-Shani
authors.forename: Ayelet
authors.initials: A
authors.lastname: Itzhaki-Alfia
authors.forename: Natalie
authors.initials: N
authors.lastname: Landa-Rouben
authors.forename: David
authors.initials: D
authors.lastname: Kain
authors.forename: Radka
authors.initials: R
authors.lastname: Holbova
authors.forename: Shimrit
authors.initials: S
authors.lastname: Adutler-Lieber
authors.forename: Natali
authors.initials: N
authors.lastname: Molotski
authors.forename: Elad
authors.initials: E
authors.lastname: Asher
authors.forename: Avishay
authors.initials: A
authors.lastname: Grupper
authors.forename: Eran
authors.initials: E
authors.lastname: Millet
authors.forename: Ariel
authors.initials: A
authors.lastname: Tessone
authors.forename: Eyal
authors.initials: E
authors.lastname: Winkler
authors.forename: Jens
authors.initials: J
authors.lastname: Kastrup
authors.forename: Micha S
authors.initials: MS
authors.lastname: Feinberg
authors.forename: Dov
authors.initials: D
authors.lastname: Zipori
authors.forename: Meirav
authors.initials: M
authors.lastname: Pevsner-Fischer
authors.forename: Ehud
authors.initials: E
authors.lastname: Raanani
authors.forename: Jonathan
authors.initials: J
authors.lastname: Leor
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006321:Heart; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells; D051379:Mice; D009203:Myocardial Infarction / Q000601:surgery; D017202:Myocardial Ischemia / Q000209:etiology; D009206:Myocardium / Q000166:cytology*; D010496:Pericardium / Q000166:cytology*
keywords: adipose tissue; epicardial fat; heart regeneration; inflammation; macrophages; mesenchymal stromal/stem cells; myocardial infarction